Pyruvate carboxylase from a variety of sources and transcarboxylase from propionibacteria are biotin enzymes with complex quaternary structures. The purpose of this investigation is to investigate the structure of these enzymes by electron microscopy. These enzymes are so large and complex that it is unlikely that it will be possible to establish their three dimensional structure by x-ray crystallography within the near future and electron microscopy is the only practical means available at present to establish this structure. Toward this end antibodies to biotin, to amino acid sequences at the substrate and binding site, and to the subunits will be prepared. These antibodies will be complexed with the subunits or enzymes and these structures will be determined in the electron microscope. From the position of the antibodies on the subunits of the enzyme, the location of the specific sites on the subunits will be determined and their relationship to the quaternary structure of the enzymes. In addition, cross linking reagents will be used to stabilize the enzymes so that they may be visualized more readily in the electron microscope. Furthermore, the cross linked enzyme will be dissociated and the subunits which are cross linked will be examined in the electron microscope as a means of interpreting the orientation of the subunits in relation to the structure of the enzymes. Other examples of investigations which will be done by electron microscopy are presented briefly.